Comparison of Early Treatment Diabetic Retinopathy Study Standard 7-Field Imaging With Ultrawide-Field Imaging for Determining Severity of Diabetic Retinopathy

Abstract

Importance: Moderate to substantial agreement between Early Treatment Diabetic Retinopathy Study (ETDRS) 7-field imaging and ultrawide-field (UWF) imaging has been suggested in single-center studies. Comparing images obtained by multiple centers could increase confidence that UWF images can be used reliably in place of ETDRS imaging in future clinical trials.

Objective: To compare diabetic retinopathy (DR) severity from modified ETDRS 7-field imaging and UWF imaging.

Design, setting, and participants: This preplanned, cross-sectional analysis included modified ETDRS 7-field images obtained using the Diabetic Retinopathy Clinical Research Network acquisition protocol and UWF images obtained captured with the Optos 200Tx system (Optos, PLC) from adult participants (≥18 years old) with type 1 or type 2 diabetes. Both image types were evaluated by trained graders masked to clinical data. Data collection occurred from February 2015 to December 2015, and data analysis from June 2016 to December 2017.

Main outcomes and measures: Agreement between UWF images, UWF images masked to include only the ETDRS 7-field area, and ETDRS 7-field images were calculated using κ statistics.

Results: A total of 764 eyes from 385 participants were included; participants had a median (IQR) age of 62.2 (53.6-69.2) years, 194 (50.4%) were women, and 256 (66.5%) were white. Of 742 eyes with both ETDRS 7-field images and UWF masked images graded, 359 (48.4% [95% CI, 44.4%-52.4%]) eyes had exact agreement, and 653 eyes (88.0% [95% CI, 85.2%-90.3%]) agreed within 1 step (weighted κ, 0.51 [95% CI, 0.44-0.58]). After open adjudication by an independent senior grader of all images with more than a 2-step discrepancy, perfect agreement was found in 435 eyes (59.0% [95% CI, 55.1%-62.8%]) and agreement within 1 step in 714 eyes (96.9% [95% CI, 95.1%-98.0%]; κ, 0.77 [95% CI, 0.73-0.82]). Ability of the imaging modalities to detect retinopathy severity in an individual eye was considered similar in 59 eyes (50.9% [95% CI, 41.3%-60.4%]), better for ETDRS 7-field imaging in 22 eyes (19.0% [95% CI, 12.5%-27.7%]), and better for UWF-masked images in 31 eyes (26.7% [95% CI 18.8%-36.5%]). Comparing UWF masked and unmasked images, 94 of 751 eyes (12.5%) had DR graded as at least 1 step more severe on UWF unmasked images vs UWF masked images. Predominantly peripheral DR lesions were present in 308 of 751 eyes (41.0%); this suggested increased DR severity by 2 or more steps in 34 eyes (11.0%).

Conclusions and relevance: Imaging by the ETDRS 7-field and UWF imaging systems have moderate to substantial agreement when determining the severity of DR within the 7 standard fields. Disparities in an individual eye are equivalently distributed between imaging modalities and can be better or worse on 1 or the other. Longitudinal follow-up will evaluate the primary outcome of this study to determine if peripheral retinal findings are associated with future retinopathy outcomes.

Conflict of interest statement

Conflict of Interest Disclosures: Dr Glassman reports receiving grants from National Institutes of Health, Allergan, and Genentech. Dr Jampol reports a grant from the National Eye Institute. Dr Kiss reports grants and personal fees from Optos and personal fees from Alimera, Alcon, Adverum, Regeneron, Novartis, Genentech, Spark, RegenXBio, and Fortress Bio. Ms Melia reports grants from the National Eye Institute and the Juvenile Diabetes Research Foundation during the conduct of the study and personal fees from National Eye Institute and other support from Vindico outside the submitted work. Dr Sun reports nonfinancial support from Optovue, Boston Micromachines, Novartis, Novo Nordisk, Adaptive Sensory Technologies, and Genentech; grants from Genentech, Juvenile Diabetes Research Foundation, and Kalvista; and personal fees from Eleven Biotherapeutics, Vindico Medical Education, Current Diabetes Reports, Merck, Allergan, Kowa, Novartis, Regeneron, and Bayer. Additionally, a complete list of all DRCR.net investigator financial disclosures is at http://drcrnet.jaeb.org.

Figures

Figure 1.. Ultrawide-Field Imaging and Masking

Ultrawide-field (200°) images from the Optos 200Tx (Optos, PLC): A, Image periphery masked such that only the idealized Early Treatment of Diabetic Retinopathy Study (ETDRS) 7-field area is visible; B, Ultrawide-field unmasked (200°) view.

Figure 2.. Differences in Diabetic Retinopathy Severity Grade Between Early Treatment of Diabetic Retinopathy Study (ETDRS) 7-Field and Ultrawide-Field Masked (UWF) Images

Differences in diabetic retinopathy severity grade on the derived 8-point scale, excluding all eyes that could not be graded by either the ETDRS 7-field photographs, the UWF masked photographs, or both. A, No difference accounted for 48.4% of the total; ETDRS 1 step worse, 16.7%; ETDRS 2 or more steps worse, 5.8%; UWF masked images 1 step worse, 22.9%; UWF masked images 2 or more steps worse, 6.2%. B, No difference accounted for 59.0% of the total; ETDRS 1 step worse, 15.2%; ETDRS 2 or more steps worse, 1.5%; UWF masked images 1 step worse, 22.7%; UWF masked images 2 or more steps worse, 1.6%.

Figure 3.. Location of Observed Lesions on Ultrawide-Field Unmasked Images

Percentage of fields with lesions observed within the Early Treatment of Diabetic Retinopathy Study (ETDRS) area, outside the ETDRS area, and uniformly distributed (approximately equivalent) within and outside the ETDRS area. The total number of fields with any lesion observed is also presented. With respect to any lesion (n = 4504), those predominantlywithin the ETDRS 7 fields was 51.3%, those uniformly distributed were 34.0%, and those predominantly outside the ETDRS fields were 14.7%. For hemorrhage or microaneurysms (n = 3056), those values were 46.0%, 39.0%, and 15.0%, respectively; for intraretinal microvascular abnormalities (n = 1299), 63.3%, 23.8%, and 12.9%, respectively; for venous beading (n = 110), 63.6%, 24.6%, and 11.8%, respectively; for new vessels elsewhere (n = 39), 33.3%, 12.8%, and 53.9%, respectively.